Transcriptogram analysis reveals relationship between viral titer and gene sets responses during Corona-virus infection
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Abstract
To understand the difference between benign and severe outcomes after Coronavirus infection, we urgently need ways to clarify and quantify the time course of tissue and immune responses. Here we re-analyze 72-hour time-series microarrays generated in 2013 by Sims and collaborators for SARS-CoV-1 in vitro infection of a human lung epithelial cell line. Transcriptograms, a Bioinformatics tool to analyze genome-wide gene expression data, allow us to define an appropriate context-dependent threshold for mechanistic relevance of gene differential expression. Without knowing in advance which genes are relevant, classical analyses detect every gene with statistically-significant differential expression, leaving us with too many genes and hypotheses to be useful. Using a Transcriptogram-based top-down approach, we identified three major, differentially-expressed gene sets comprising 219 mainly immune-response-related genes. We identified timescales for alterations in mitochondrial activity, signaling and transcription regulation of the innate and adaptive immune systems and their relationship to viral titer. The methods can be applied to RNA data sets for SARS-CoV-2 to investigate the origin of differential responses in different tissue types, or due to immune or preexisting conditions or to compare cell culture, organoid culture, animal models and human-derived samples.
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SciScore for 10.1101/2020.06.16.155267: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources STRING uses seven different methods to infer whether two proteins are associated, ranging from physical interactions, information retrieved from (reliable) data bases like HUGO, to co-expression, experiments, etc.. STRINGsuggested: (STRING, RRID:SCR_005223)HUGOsuggested: (HUGO, RRID:SCR_012800)1 shows term-enrichment profiles projected on the ordered list, obtained for selected KEGG pathways and Gene Ontology: Biological function terms (GO:BP). KEGGsuggested: (KEGG, RRID:SCR_012773)Ontology: Biologicalsuggested: NoneResults from OddPub: Thank you for sharing your data.
Results from Limitation…SciScore for 10.1101/2020.06.16.155267: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Software and Algorithms Sentences Resources STRING uses seven different methods to infer whether two proteins are associated, ranging from physical interactions, information retrieved from (reliable) data bases like HUGO, to co-expression, experiments, etc.. STRINGsuggested: (STRING, RRID:SCR_005223)HUGOsuggested: (HUGO, RRID:SCR_012800)1 shows term-enrichment profiles projected on the ordered list, obtained for selected KEGG pathways and Gene Ontology: Biological function terms (GO:BP). KEGGsuggested: (KEGG, RRID:SCR_012773)Ontology: Biologicalsuggested: NoneResults from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 14. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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